U.S. Pat. Nos. 5,193,551 and 6,415,642 B1 describe a method and apparatus for calibrating an apparatus for measuring a diffusion capacity of a person's lungs.
Apparatuses for measuring a diffusion capacity of a person's lungs are known per se. In particular Oxygen diffusion is an important clinical measure. The rate of Oxygen diffusion from the lungs to the blood depends on diffusion capacity, and the difference between the Oxygen pressure in the blood and the alveolar space of the lungs. In clinical laboratories, lung diffusion capacity is usually measured for carbon monoxide (CO) instead of Oxygen. The reason is the very high affinity of CO for hemoglobine, which helps to keep the CO pressure in the capillary blood negligible small compared to the CO pressure in the alveolar space. Consequently, unlike the O2 diffusion capacity, the CO diffusion capacity (DLCO) can be determined non-invasively, because the pressure in the blood does not need to be measured. This is an important advantage in clinical routine. The membrane diffusion capacities DLO2 and DLCO appear to have comparable diagnostic values. Therefore, the use of CO as a test gas for measuring diffusion capacity has become standard clinical practice.
Various measurement techniques exist to measure DLCO, such as single breath, multiple breath, re-breathing and steady state methods. For many decades, the single breath (SB) technique has become the technique of choice in nearly all lung function departments and laboratories all over the word. SB machines are commercially available from several manufacturers. Good medical practice requires that these machines have to be maintained and kept in good conditions. So there is a strong need for proper devices to evaluate the machines, in an easy and uncomplicated manner (As used herein “evaluation” is any process that results in information about the operation of the DLCO measuring apparatus. Calibrating and testing are examples of “evaluating” as used herein).
Typically the procedure of a DLCO measurement with a SB machine is as follows. A person connected to the SB machine is ordered first to expire maximally so that a residual volume (V0, initial volume) remains in the lung, then immediate afterwards to inhale maximally. At the end of the volume inhaled (VI) the patient keeps his breath during a certain breath hold time (BHT). The lung volume at breath hold time is V0+VI. The breath hold time can be for example 10 seconds. During the inhalation phase the SB machine provides a gas mixture containing test gas components which the patient inhales into his lungs; the test gas components are CO and an inert reference gas (inert gas, IG) like He, Ne, or CH4, both with known, pre-adjusted, concentrations.
Once the patient has inhaled the gas mixture, the inert gas will be diluted by the residual volume of air mixture in the lungs that remains in the lungs all the time, while the CO, after dilution like the inert gas, and after diffusing to the bloodstream, is carried away by the bloodstream. Thus, in the lungs, the relative decrease of CO is greater then that of the inert gas IG. After the breath hold time the patient exhales, an alveolar sample of the exhaled gas is collected by the SB-machine where it is analysed for CO- and inert gas concentration.
This results in the quantitative measurements of diffusion capacity using the following considerations, Quantities VI, BHT, rCO and rIG are measured. rIG is the ratio of measurements of exhalation and inhalation concentration of the inert gas IG. rCO is the ratio of measurements of those concentrations of CO. VI is the inhaled/exhaled volume and BHT is the breath hold time. The condition for diffusion in the lung can then be stated as rCO<rIG<1. During the breath hold time CO disappears through diffusion through the membrane, and as a result its concentration decreases in time. Assuming that the lung consists of one single alveolar compartment, this decrease has an exponential shape because the disappearance rate is proportional to the concentration gradient across the membrane, and this is changing continuously.
DLCO is obtained from the measurement data asDLCO=−1/(R*T)*ln(rCO/rIG)/BHT*VI/rIG  (1)
where R is the gas constant and T is absolute temperature in the lung (for example 310K), and “ln” refers to the Naperian logarithm.
Unfortunately the apparatus for measuring DLCO can malfunction, which can lead to erroneous DLCO results, for example when the determination of CO concentration, IG concentration or the volume VI suffers from errors. Therefore reliable computation of DLCO requires evaluating of the apparatus for measuring DLCO that uses the SB technique, to verify that it produces the correct results. U.S. Pat. No. 5,193,551 and U.S. Pat. No. 6,415,642 describe this type of evaluating. Both devices uses a large-volume syringe (gas cylinder with piston) to simulate the volume and volume changes of the lungs. The mouth of the syringe is connected to the mouth connection of the SB apparatus under evaluation. The volume of the internal syringe space is changed manually by a technician in the same sequence as for the SB technique (as described above), including an inhalation phase, a breath holding phase, and an exhalation phase. Both these devices intentionally modify the concentrations of inert gas and CO in the exhaled gas mixture; in such a manner that the resulting concentrations satisfy the above-mentioned conditions for CO-diffusion.
U.S. Pat. No. 5,193,551 describes a calibration device using a syringe that is connected via a special purpose inter-space chamber with the SB-test machine. On some time before, a certain amount of the used inert gas is brought into the inter-space chamber. During the inhalation phase the gas mixture supplied by the machine (containing CO and inert gas) flows through the inter-space chamber into the syringe volume space, thereby taking up some of the inert gas initially present in the inter-space chamber. So, besides the volumetric dilution of the CO and inert gas, the inert gas is subjected to an additional increase. During the exhalation phase the gas in the syringe space is returned directly, without streaming through the inter-space chamber, to the evaluation machine. The resulting exhaled/inhaled concentration ratios then satisfy the condition rCO<rIG<1, signifying that CO-diffusion has validly been simulated. After analysis and subsequent calculations in the evaluation machine using a similar formula as equation (1), a DLCO-value can be predicted.
A critical point of this device is the precise prediction of the fractional reduction ratios rIG and rCO. These ratios depend on the precise amount of dilution in the inter-space chamber, which in turn will depend on the particular state of gas flow and convection in the inter-space chamber (be it plug flow, ideal mixing, or some intermediate state between). However, the document supplies no information how to predict these ratios from the dilution process. Assuming that the dilution process in the inner-space chamber behaves reproducibly, the resulting simulated DLCO value will be reproducible as well, which would make this device still useful as a relative DLCO calibrator,
U.S. Pat. No. 6,415,642 describes a calibration device using two syringes. The SB machine under evaluation is connected with the first syringe with which the inhalation phase is simulated. A short time before the start of the exhalation phase the other syringe is connected to the evaluation-machine. This second syringe has been filled with a test gas mixture containing CO and inert gas with precisely known concentrations that are carefully chosen so as to satisfy the condition rCO<rIG<1. In that case the SB machine can produces valid simulated DLCO values, useful for test- and calibration purposes.
In both patents the obtained DLCO-value depends on several parameters: the supplied inhaled volume, the CO and inert gas concentration in the machine gas mixture as well as in the required precision test gas mixture. This makes calibration complex and sensitive to errors in these parameters. Moreover, these calibrators can only be used for testing SB-equipment.